Clinical investigations are underway to determine the early natural history of senile macular degeneration. Drusen and serous and hemorrhagic detachments of the retina and retinal pigmented epithelium, as well as choroidal neovascularization, are considered manifestations of senile macular degeneration and will be studied by serial recordings of the anatomical appearance and visual functioning of eyes at high risk of developing disease. These results will be compared with those obtained from fellow eyes with more advanced disease, age matched normals, and those with other maculopathies including that of retinitis pigmentosa. Serum, and in some cases, 24 hour urine, levels of hormones including melatonin, cortisol, thyroid and trace metal ions are being determined. By emphasizing studies of members of affected family clusters and using various genetic markers such as HLA antigens to segregate the affected from the unaffected members, it is hoped that those factors materially associated with the appearance and/or progression of various retinal degenerative conditions will be elucidated.